The Antibody Initiative Antivenom

The bite or sting of a highly venomous animal can inflict great suffering, including loss of limbs, paralysis, and an extremely painful death. In the United States, envenomation (the injection of venom) usually happens during an encounter with a snake, spider, or insect.

Antivenom (often spelled “antivenin”) is an antibody product that can disable a particular venom’s toxins. If injected quickly after a bite or sting, the antibodies in antivenom neutralize the venom, potentially saving the victim’s life or limb.

Antivenom is still produced by much the same method that was developed in the 1890s to produce antitoxins for diphtheria and tetanus. An animal, such as a horse or goat, is injected with a small amount of venom. The antibodies released by the animal’s immune system to fight the damaging venom are later harvested via bleeding. The blood serum or plasma is then concentrated and purified into pharmaceutical-grade antivenom.

Although Antivenom can prevent venom-induced damage to a body, it is less able to reverse damage already wreaked by the venom. Thus, it is important that antivenom treatment start as quickly as possible. Depending on the amount and toxicity of the venom, a victim may need many injections of antivenom to sufficiently neutralize the venom.

Antivenom must be tailored to combat the venom of a particular species. The museum’s collection contains examples of antivenoms that were produced specifically to treat bites and stings of those venomous creatures endemic to the United States.

The French scientist Albert Calmette developed the first antivenom by 1895 (against the venom of the cobra). It would be another 30 years before antivenom was produced in the United States. In 1927, the H. K. Mulford Company of Philadelphia advertised that they were the first company licensed to produce and sell antivenom in the United States. They had partnered with the Brazilian developer of the antivenom, Dr. Afriano do Amaral of the Antivenin Institute of America. Amaral supervised the collection and purification of venom from the Institute’s snakes. The venom was then sent to Mulford Laboratories, where it was injected into the company’s horses to produce the antivenom.

Mulford’s initial antivenom product—Antivenin Nearctic Crotalidae—treated bites of North American pit vipers, including rattlesnakes, moccasins, and copperheads. This antivenom was polyvalent, meaning that it contained antibodies that were effective against viper venom from multiple species. In 1929, the museum collected a specimen of Antivenin Nearctic Crotalidae from the Mulford Company as part of an exhibition of new serum therapies.

In 1927, the Journal of the National Medical Association celebrated the introduction of Mulford’s North American pit viper antivenom, proclaiming, “A package of Antivenin should be included in every first-aid kit.” Mulford’s advertising materials claimed that antivenom was a necessary “insurance” for all those at risk of snake-bite, and warned that children at play, fishermen and hunters, farmers, civil engineers, and utility workers were all likely candidates for bites. The company stated that children’s camps, military camps, and construction sites all had a duty to keep antivenom on hand. Antivenom was an exciting new technology that offered hope in the face of a common human fear. In 1930, the museum again collected from the Mulford Company for an exhibition illustrating the manufacture and use of “anti-snake-bite serum.”

By this time, the H. K. Mulford Company offered two additional varieties of snake antivenom. The first, Antivenin Bothropic, was another polyvalent antivenom created to neutralize the venom of South American pit vipers of the genus Bothrops. Bites from these snakes kill more people in the Americas than any other venomous snake. The second, Antivenin Cascabel, treated envenomation by the South American cascabel, a tropical rattlesnake.

 

A Bothropic Antivenin kit from 1930. Mulford supplied its antivenom in pre-filled syringe kits to make treatments easy to transport and administer when one was far from medical attention. According to the kit’s directions, immediately following a snakebite, you must inject the entire contents of the syringe under the skin of your thigh or abdomen. Even better, a companion could inject you in the arm or between the shoulder blades.

Mulford Laboratories expanded into the spider bite business in 1936, when they produced an antivenom against Latrodectus mactans—the black widow spider.

In the past few years, snakebite antivenom has been in the news, again. In states such as Texas and Florida, a shortage of coral snake antivenom has put medical providers in a disturbing position. Because they do not want to waste the precious treatment, some doctors feel pressured to wait and see if a bite-victim shows symptoms of envenomation before administering antivenom. However, the power of the treatment can be compromised by waiting.

Although the World Health Organization includes snakebite antivenom on its List of Essential Medicines, the world is experiencing shortages of antivenom. The populations hardest hit by the shortages tend to live and work in rural areas where highly venomous snakes are endemic, especially in less-developed nations with housing that allows for easier access by venomous snakes.

Hospitals currently face a multifaceted antivenom problem. Antivenom can be very expensive, a problem that is compounded when the product goes unused before its expiration date. Many clinics do not have sufficient training in selecting the correct antivenom or administering the treatment. The challenges do not stop there: patients can suffer serious allergic reactions to antivenom, and medical supervision during treatment is important.

New monoclonal antibody antivenoms that cause fewer allergic reactions are being developed. Like Mulford’s initial 1927 antivenom product, CroFab antivenom is an antidote to the venom of North American pit vipers, including rattlesnake, cottonmouth, and copperhead. However, because the CroFab product uses only a fragment of the cultured antibody, it causes fewer serious allergic reactions than older serum-based, whole antibody antivenoms. 

Antivenom is one of those treatments that most of us never think about—until we suddenly and very desperately need it. The American Medical Association’s 1927 prediction that antivenom should be in every first-aid kit has not come to be. Contemporary antivenoms made under strict controls are very effective. Yet, they remain out of reach for many victims who most need them.